Determination of the absolute configuration of aromatase and dual aromatase-sulfatase inhibitors by vibrational and electronic circular dichroism spectra analysis

The absolute configuration of a newly designed, letrozole-based chiral
aromatase inhibitor that could not be defined by crystallographic techniques has been
determined by means of vibrational and electronic circular dichroism and by optical
rotation measurements combined with density functional theory calculations on possible
conformers. The same absolute configurational assignment can be applied to the individual
enantiomeric sulfamate esters, which are derived from the corresponding enantiomers
of the chirally separated parent phenols, based on the similarity of the ECD
spectrum of the sulfamate derivative to that of its phenolic precursor. The two enantiomeric
sulfamate esters studied here are the first examples of nonsteroidal dual aromatase-
sulfatase inhibitor whose activities have been evaluated on optically resolved enantiomers.